DESCRIPTION: This proposal has as its focus the structural and functional role of the ubiquitously distributed cysteine-rich metal binding protein metallothionein (MT). MT was discovered 38 years ago, but its physiological role remains unconfirmed. However, its biosynthesis is closely regulated by exposure to heavy metal ions and in combination with extensive experimental data on metal binding, has lead to a proposal that MT is a critical component in metal homeostasis. A central focus of this work will be to determine 3D solution structures of three MTs, one mammalian, one from Neurospora crassa and one from the blue Crab. In previous studies unique metal-ion lability has been demonstrated for the 3-metal cluster in beta domain. It was demonstrated that intermolecular exchange occurs between beta-sites, and another goal of this proposal is to elucidate the mechanistic and kinetic details of this metal exchange phenomenon.